A mouse model for visualization of GABA_B receptors

GABA_B receptors are the G-protein-coupled receptors for the neurotransmitter γ-aminobutyric acid (GABA). Receptor subtypes are based on the subunit isoforms GABA_B1a and GABA_B1b, which combine with GABA_B2 subunits to form heteromeric receptors. Here, we used a modified bacterial artificial chromosome (BAC) containing the GABA_B1 gene to generate transgenic mice expressing GABA_B1a and GABA _B1b subunits fused to the enhanced green fluorescence protein (eGFP). We demonstrate that the GABA_B1-eGFP fusion proteins reproduce the cellular expression patterns of endogenous GABA_B1 proteins in the brain and in peripheral tissue. Crossing the GABA_B1-eGFP BAC transgene into the GABA_B1 ^-/- background restores pre and postsynaptic GABA_B functions, showing that the GABA_B1-eGFP fusion proteins substitute for the lack of endogenous GABA_B1 proteins. Finally, we demonstrate that the GABA_B1-eGFP fusion proteins replicate the temporal expression patterns of native GABA_B receptors in cultured neurons. These transgenic mice therefore provide a validated tool for direct visualization of native GABA_B receptors.